Cissen Maartje, Bensdorp Alexandra, Cohlen Ben J, Repping Sjoerd, de Bruin Jan Peter, van Wely Madelon
Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Henri Dunantstraat 1, PO Box 90153, 's-Hertogenbosch, Netherlands, 5200 ME.
Cochrane Database Syst Rev. 2016 Feb 26;2(2):CD000360. doi: 10.1002/14651858.CD000360.pub5.
Intra-uterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are frequently used fertility treatments for couples with male subfertility. The use of these treatments has been subject of discussion. Knowledge on the effectiveness of fertility treatments for male subfertility with different grades of severity is limited. Possibly, couples are exposed to unnecessary or ineffective treatments on a large scale.
To evaluate the effectiveness and safety of different fertility treatments (expectant management, timed intercourse (TI), IUI, IVF and ICSI) for couples whose subfertility appears to be due to abnormal sperm parameters.
We searched for all publications that described randomised controlled trials (RCTs) of the treatment for male subfertility. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO and the National Research Register from inception to 14 April 2015, and web-based trial registers from January 1985 to April 2015. We applied no language restrictions. We checked all references in the identified trials and background papers and contacted authors to identify relevant published and unpublished data.
We included RCTs comparing different treatment options for male subfertility. These were expectant management, TI (with or without ovarian hyperstimulation (OH)), IUI (with or without OH), IVF and ICSI. We included only couples with abnormal sperm parameters.
Two review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the review authors. We performed statistical analyses in accordance with the guidelines for statistical analysis developed by The Cochrane Collaboration. The quality of the evidence was rated using the GRADE methods. Primary outcomes were live birth and ovarian hyperstimulation syndrome (OHSS) per couple randomised.
The review included 10 RCTs (757 couples). The quality of the evidence was low or very low for all comparisons. The main limitations in the evidence were failure to describe study methods, serious imprecision and inconsistency. IUI versus TI (five RCTs)Two RCTs compared IUI with TI in natural cycles. There were no data on live birth or OHSS. We found no evidence of a difference in pregnancy rates (2 RCTs, 62 couples: odds ratio (OR) 4.57, 95% confidence interval (CI) 0.21 to 102, very low quality evidence; there were no events in one of the studies).Three RCTs compared IUI with TI both in cycles with OH. We found no evidence of a difference in live birth rates (1 RCT, 81 couples: OR 0.89, 95% CI 0.30 to 2.59; low quality evidence) or pregnancy rates (3 RCTs, 202 couples: OR 1.51, 95% CI 0.74 to 3.07; I(2) = 11%, very low quality evidence). One RCT reported data on OHSS. None of the 62 women had OHSS.One RCT compared IUI in cycles with OH with TI in natural cycles. We found no evidence of a difference in live birth rates (1 RCT, 44 couples: OR 3.14, 95% CI 0.12 to 81.35; very low quality evidence). Data on OHSS were not available. IUI in cycles with OH versus IUI in natural cycles (five RCTs)We found no evidence of a difference in live birth rates (3 RCTs, 346 couples: OR 1.34, 95% CI 0.77 to 2.33; I(2) = 0%, very low quality evidence) and pregnancy rates (4 RCTs, 399 couples: OR 1.68, 95% CI 1.00 to 2.82; I(2) = 0%, very low quality evidence). There were no data on OHSS. IVF versus IUI in natural cycles or cycles with OH (two RCTs)We found no evidence of a difference in live birth rates between IVF versus IUI in natural cycles (1 RCT, 53 couples: OR 0.77, 95% CI 0.25 to 2.35; low quality evidence) or IVF versus IUI in cycles with OH (2 RCTs, 86 couples: OR 1.03, 95% CI 0.43 to 2.45; I(2) = 0%, very low quality evidence). One RCT reported data on OHSS. None of the women had OHSS.Overall, we found no evidence of a difference between any of the groups in rates of live birth, pregnancy or adverse events (multiple pregnancy, miscarriage). However, most of the evidence was very low quality.There were no studies on IUI in natural cycles versus TI in stimulated cycles, IVF versus TI, ICSI versus TI, ICSI versus IUI (with OH) or ICSI versus IVF.
AUTHORS' CONCLUSIONS: We found insufficient evidence to determine whether there was any difference in safety and effectiveness between different treatments for male subfertility. More research is needed.
宫腔内人工授精(IUI)、体外受精(IVF)和卵胞浆内单精子注射(ICSI)是治疗男性生育力低下夫妇常用的辅助生殖技术。这些技术的应用一直存在争议。目前对于不同严重程度男性生育力低下的治疗效果的了解有限。可能会导致夫妇在很大程度上接受了不必要或无效的治疗。
评估不同辅助生殖技术(期待治疗、定时性交(TI)、IUI、IVF和ICSI)对因精子参数异常导致生育力低下夫妇的有效性和安全性。
检索所有描述男性生育力低下治疗的随机对照试验(RCT)。检索Cochrane月经紊乱与生育力低下小组专业注册库、Cochrane对照试验中心注册库(CENTRAL)、MEDLINE、EMBASE、CINAHL、PsycINFO和国家研究注册库,检索时间从建库至2015年4月14日,并检索1985年1月至2015年4月的基于网络的试验注册库。检索无语言限制。检查纳入试验和背景文献中的所有参考文献,并联系作者以识别相关的已发表和未发表数据。
纳入比较男性生育力低下不同治疗方案的RCT。这些方案包括期待治疗、TI(有或无卵巢过度刺激(OH))、IUI(有或无OH)、IVF和ICSI。仅纳入精子参数异常的夫妇。
两位综述作者独立选择研究、提取数据并评估偏倚风险。他们通过与其他综述作者讨论解决分歧。我们按照Cochrane协作网制定的统计分析指南进行统计分析。使用GRADE方法对证据质量进行评级。主要结局是每对随机分组夫妇的活产和卵巢过度刺激综合征(OHSS)。
该综述纳入10项RCT(757对夫妇)。所有比较的证据质量均为低或极低。证据的主要局限性在于未描述研究方法、严重不精确和不一致。IUI与TI比较(5项RCT):两项RCT在自然周期中将IUI与TI进行比较。无活产或OHSS数据。我们未发现妊娠率有差异的证据(2项RCT,62对夫妇:比值比(OR)4.57,95%置信区间(CI)0.21至102,极低质量证据;其中一项研究无事件发生)。三项RCT在OH周期中将IUI与TI进行比较。我们未发现活产率有差异的证据(1项RCT,81对夫妇:OR 0.89,95%CI 0.30至2.59;低质量证据)或妊娠率有差异的证据(3项RCT,202对夫妇:OR 1.51,95%CI 0.74至3.07;I² = 11%,极低质量证据)。一项RCT报告了OHSS数据。62名女性中无一例发生OHSS。一项RCT将OH周期中的IUI与自然周期中的TI进行比较。我们未发现活产率有差异的证据(1项RCT,44对夫妇:OR 3.14,95%CI 0.12至81.35;极低质量证据)。无OHSS数据。OH周期中的IUI与自然周期中的IUI比较(5项RCT):我们未发现活产率(3项RCT,346对夫妇:OR 1.34,95%CI 0.77至2.33;I² = 0%,极低质量证据)和妊娠率(4项RCT,399对夫妇:OR 1.68,95%CI 1.00至2.82;I² = 0%,极低质量证据)有差异的证据。无OHSS数据。自然周期或OH周期中IVF与IUI比较(2项RCT):我们未发现自然周期中IVF与IUI活产率有差异的证据(1项RCT,53对夫妇:OR 0.77,95%CI 0.25至2.35;低质量证据),或OH周期中IVF与IUI活产率有差异的证据(2项RCT,86对夫妇:OR 1.03,95%CI 0.43至2.45;I² = 0%,极低质量证据)。一项RCT报告了OHSS数据。女性中无一例发生OHSS。总体而言,我们未发现任何组间在活产率、妊娠率或不良事件(多胎妊娠、流产)发生率上有差异的证据。然而,大多数证据质量极低。未对自然周期中的IUI与刺激周期中的TI、IVF与TI、ICSI与TI、ICSI与IUI(有OH)或ICSI与IVF进行研究。
我们没有足够的证据来确定不同男性生育力低下治疗方法在安全性和有效性上是否存在差异。需要更多的研究。